Small lesion size measured by colposcopy may predict absence of cervical intraepithelial neoplasia in a large loop excision of the transformation zone specimen.

OBJECTIVE: To evaluate whether colposcopic measurement of the lesion size at diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in women treated for squamous intraepithelial lesions/cervical intraepithelial neoplasia (SIL/CIN). DESIGN: Prospective observational study. SETTING: Tertiary university hospital. POPULATION: A cohort of 116 women who underwent LLETZ because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or because of a high-grade SIL/CIN diagnosed in the referral visit and squamocolumnar junction completely visible (types 1 or 2, according to the International Federation of Cervical Pathology and Colposcopy, IFCPC). METHODS: After LLETZ the women were classified by histology into the study group (absence of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group (SIL/CIN in the LLETZ specimen, 88/116, 75.9%). MAIN OUTCOME MEASURES: The size of the lesion determined in the diagnostic colposcopy and the HPV genotype were evaluated in all women. RESULTS: The lesion size was significantly smaller in the study group (25.7 ± 37.8 versus 84.5 ± 81.7 mm2 ; P < 0.001). A lesion size of ≤12 mm2 and HPV types other than 16 or 18 were associated with an absence of SIL/CIN in the LLETZ specimen (P < 0.001 and P = 0.016, respectively). On multivariate analysis only a lesion size of ≤12 mm2 predicted the absence of SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P < 0.001). A lesion size of ≤12 mm2 had a specificity of 90.9% (95% CI 83.0-95.3%) and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the absence of SIL/CIN in the surgical specimen. CONCLUSIONS: Small lesion size in diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen. Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary treatment. TWEETABLE ABSTRACT: Small lesion size in colposcopic evaluation might predict the absence of SIL/CIN in an LLETZ specimen.

HPV testing in first-void urine provides sensitivity for CIN2+ detection comparable with a smear taken by a clinician or a brush-based self-sample: cross-sectional data from a triage population.

OBJECTIVE: To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. DESIGN: Cross-sectional single-centre study. SETTING: A colposcopy clinic in Spain. POPULATION: A cohort of 113 women referred for colposcopy after an abnormal Pap smear. METHODS: Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. MAIN OUTCOME MEASURES: Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. RESULTS: Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10-14% discordance on hrHPV genotype. CONCLUSIONS: CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. TWEETABLE ABSTRACT: Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis.

OBJECTIVE: Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)-negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV-negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV-negativity. DESIGN: Observational study. SETTING: Barcelona, Spain. POPULATION: A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre-treatment HC2 testing. METHODS: All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7-specific assay). MAIN OUTCOME MEASURES: Percentage of confirmed HPV-negative and HPV-positive tumours. Clinicopathological features and disease-free survival (DFS) and overall survival (OS) of both groups. RESULTS: Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR-based techniques only 8/136 (5.8%) tumours were confirmed as HPV-negative, whereas in six cases different HPVs were identified [HPV-11, -16 (two tumours), -18, -45, and -68]. Confirmed HPV-negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV-negativity had significantly worse DFS than women with HPV-positive tumours [51.9 months (95% CI 12.2-91.7 months) versus 109.9 months (95% CI 98.2-121.5 months); P = 0.010]. In the multivariate analysis HPV-negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality. CONCLUSIONS: An HC2-negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV-negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.

Interlaboratory reproducibility and proficiency testing within the human papillomavirus cervical cancer screening program in Catalonia, Spain.

In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P<0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention.

The increased detection of cervical intraepithelial neoplasia when using a second biopsy at colposcopy.

OBJECTIVE: It has been suggested that colposcopy can miss a significant percentage of high-grade cervical intraepithelial neoplasia (CIN2+). Improved disease ascertainment was evaluated by taking multiple lesion-directed biopsies. METHODS: In a cross-sectional multicenter study in the Netherlands and Spain, 610 women referred to colposcopy following abnormal cervical cytology results were included. Multiple directed biopsies were collected from lesions and ranked according to impression. A non-directed biopsy of normal-appearing tissue was added if fewer than four biopsies were collected. We evaluated the additional CIN2+ yield for one and two directed biopsies. Colposcopic images were reviewed for quality control. RESULTS: In women with at least two lesion-directed biopsies the yield for CIN2+ increased from 51.7% (95%CI; 45.7-57.7) for one directed biopsy to 60.4% (95%CI; 54.4-66.2, p<0.001) for two biopsies. The highest CIN2+ yield was observed in women who were HPV16-positive, had high-grade squamous intraepithelial lesion (HSIL) cytology, and high-grade colposcopy impression. The yield increased from 83.1% (95%CI; 71.5-90.5) with one directed biopsy to 93.2% (95%CI; 83.8-97.3) with two directed biopsies. Only 4.5% additional CIN2+ were detected in biopsies not targeting abnormal areas on the cervix. CONCLUSIONS: A second lesion-directed biopsy is associated with a significant increase in CIN2+ detection. Performing a second lesion-directed biopsy and using a low threshold for abnormality of any acetowhitening should become the standard clinical practice of colposcopy.

The impact of human papillomavirus genotype on colposcopic appearance: a cross-sectional analysis.

OBJECTIVE: To study colposcopic performance in diagnosing high-grade cervical intraepithelial neoplasia or cervical cancer (CIN2+ and CIN3+) using colposcopic characteristics and high-risk human papillomavirus (hrHPV) genotyping. DESIGN: Cross-sectional multicentre study. SETTING: Two colposcopy clinics in The Netherlands and Spain. POPULATION: Six hundred and ten women aged 17 years and older referred for colposcopy because of abnormal cytology. METHODS: A cervical smear was obtained. Colposcopists identified the worst lesion, graded their impression and scored the colposcopic characteristics of the lesions. Up to four biopsies were collected, including one biopsy from visually normal tissue. MAIN OUTCOME MEASURES: CIN2+ and CIN3+, positive for HPV16 or other high-risk HPV types (non-16 hrHPV-positive). RESULTS: The mean age in HPV16-positive CIN2+ women was 35.1 years compared with 39.1 years in women with other hrHPV types (P = 0.002). Sensitivity for colposcopy to detect CIN2+ was 87.9% (95%CI 83.2-91.5), using colposcopic cut-off of 'any abnormality'. The remaining CIN2+ were found by a biopsy from visually normal tissue or endocervical curettage (ECC). Detection of CIN2+ by lesion-targeted biopsies was not different between HPV16-positive women [119/135; 88.1% (95%CI 81.2-92.9)] and non-16 hrHPV-positive women [100/115; 87.0% (95%CI 79.1-92.3); P = 0.776]. In multivariate analysis, 'acetowhitening' [odds ratio (OR) 1.91, 95%CI 1.56-3.17], 'time of appearance' (OR 1.95, 95%CI 1.21-3.15) and 'lesion >25% of visible cervix' (OR 2.25, 95%CI 1.44-3.51) were associated with CIN2+. CONCLUSIONS: In this population following European screening practice, HPV16-related CIN2+ lesions were detected at younger age and showed similar colposcopic impression as non-16 hrHPV high-grade lesions. There was no relationship between any of the colposcopic characteristics and HPV16 status.

Intraoperative post-conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study.

OBJECTIVE: To evaluate the feasibility and utility of intraoperative post-conisation human papillomavirus (IOP-HPV) testing and cytology to detect treatment failure in patients with cervical intraepithelial neoplasia grades 2-3 (CIN2-3). DESIGN: Prospective observational pilot study. SETTING: Barcelona, Spain. POPULATION: A cohort of 132 women treated for CIN2-3 by loop electrosurgical conisation. METHODS: An endocervical sample was obtained intraoperatively with a cytobrush from the cervix remaining after the conisation. The material was kept in PreservCyt medium and processed for Hybrid Capture 2 and cytology. Patients were followed-up for 24 months. The performance of IOP-HPV testing and IOP cytology was compared with conventional indicators of recurrence (cone margin, endocervical curettage, and HPV testing and cytology at 6 months). MAIN OUTCOME MEASURE: Treatment failure (i.e. recurrent CIN2-3 during follow-up). RESULTS: Treatment failure was identified in 12 women (9.1%). IOP-HPV testing for sensitivity, specificity, and positive and negative predictive values for treatment failure were 91.7, 78.3, 62.2, and 96.0%, respectively, which are similar to the figures for conventional HPV testing at 6 months (91.7, 76.0, 64.0, and 95.1%, respectively), and are better than the values of other conventional predictive factors (cone margin, endocervical curettage, and cytology intraoperative at 6 months). IOP-HPV was strongly associated with treatment failure in the multivariate analysis (OR 15.40, 95% CI 1.58-150.42). CONCLUSION: IOP-HPV testing is feasible, and accurately predicts treatment failure in patients with CIN2-3. This new approach may allow an early identification of patients with treatment failure, thereby facilitating the scheduling of an attenuated follow-up for negative patients who are at very low risk of persistent disease.

Laryngeal squamous cell carcinoma in HIV-positive patients: lack of association with human papillomavirus infection.

OBJECTIVES: Neoplasms associated with human papillomavirus (HPV) infection occur at increased frequency in patients with HIV infection/AIDS. Although laryngeal squamous cell carcinomas (LSCCs) in HIV-positive patients are uncommon, a higher incidence of this malignancy in HIV-positive patients than in the general population has been reported. As a proportion of LSCCs are associated with HPV in the general population, the clinicopathological features of a series of LSCCs developing in HIV-positive patients were evaluated to investigate the possible relationship with HPV infection, and infection with other oncogenic viruses. METHODS: All HIV-positive patients with LSCC diagnosed at a single institution from 1998 to 2007 were retrospectively evaluated. The clinicopathological features were analysed and tissues were tested by polymerase chain reaction (PCR), using the short PCR fragment 10 (SPF10) primer, a highly sensitive method for HPV DNA detection. Immunohistochemical studies for HIV p24, p16(INK4a) and p53 were performed. Epstein-Barr virus (EBV) and human herpes virus 8 (HHV-8) were also investigated. RESULTS: Six out of 4987 HIV-infected patients seen in this period in the Infectious Diseases Department developed LSCC (median age 41.5 years; male to female ratio 1:1). All patients were heavy smokers and the tumours presented at an advanced clinical stage. HPV was not detected in any tumour, not even in two patients with coexisting HPV-associated gynaecological neoplasm. Staining for HIV p24 and p16(INK4a) was negative, whereas p53 was positive in half the cases. EBV and HHV-8 were also negative. CONCLUSION: LSCC developing in HIV-positive patients is an infrequent neoplasm, not usually associated with HPV infection. It develops in young, heavy smokers and presents at an advanced clinical stage.

[Sentinel node in gynaecological cancers. Our experience]. / Ganglio centinela en cánceres ginecológicos. Nuestra experiencia.

UNLABELLED: Although sentinel lymph node (SLN) identification is widespread used in melanoma and breast cancer some concerns exist in other malignancies, such gynaecologic cancers, and this staging method has not been adopted in many centers due to lack or large validation studies. AIM: To evaluate the applicability and results of SLN technique in gynaecological malignancies referred to our institution. METHOD: We studied 155 patients with different malignancies (70 vulvar, 50 cervical and 35 endometrial cancers). The day before surgery a lymphoscintigraphy was performed by injecting 111 MBq of (99m)Tc-nanocolloid in several ways depending on the type of cancer studied. Intraoperative detection of the SLN was always performed by using a hand-held gammaprobe and, in 100 cases with the aid of blue dye injection (70 vulvar and 30 in cervical cancer) few minutes before surgical intervention. Pathological study of SLN was performed in all cases. Lymphadenectomy was done in all cervix and endometrial cancer patients and in the first 35 vulvar cancer patients. RESULTS: Pre-surgical lymphoscintigraphy demonstrated one, at least, SLN in 97% of vulvar cancer patients, 92% in the cervical malignancy and 64% in the endometrial cancer patients. During surgery, SLN was harvested in 97%, 90% and 62% of patients, respectively. The pathological study showed metastases in 24.2%, 8.8 and 4.5% of patients with vulvar, cervical and endometrial cancer, respectively. The false negative percentage was 5.5% in vulvar cancer patients, with 2 cases in the endometrial cancer and without any case in the cervical cancer patients. CONCLUSION: Lymphoscintigraphy is a relatively simple and useful technique to identify the SLN in this kind of tumours. However, in endometrial cancer more effort has to be made to reach a suitable result. Sentinel lymph node biopsy seems to be a reliable technique in vulvar and cervical malignancies.

Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria.

OBJECTIVES: Malaria infection may impact on mother-to-child transmission (MTCT) of HIV-1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV-1 MTCT in southern Mozambique. METHODS: A total of 207 HIV-positive Mozambican pregnant women were enrolled in the study as part of a randomized placebo-controlled trial of two-dose sulfadoxine-pyrimethamine (SP) IPTp in women receiving single-dose nevirapine to prevent MTCT of HIV. HIV RNA viral load, maternal anaemia and peripheral and placental malaria were assessed at delivery. Infant HIV status was determined by DNA polymerase chain reaction (PCR) at 1 month of age. RESULTS: There were 19 transmissions of HIV in 153 mother-infant pairs. IPTp with SP did not have a significant impact on MTCT (11.8% in the SP group vs. 13.2% in the placebo group; P=0.784) or on maternal HIV RNA viral load [16 312 (interquartile range {IQR} 4076-69 296) HIV-1 RNA copies/mL in the SP group vs. 18 274 (IQR 5471-74 104) copies/mL in the placebo group; P=0.715]. In multivariate analysis, maternal HIV RNA viral load [adjusted odds ratio (AOR) 19.9; 95% confidence interval (CI) 2.3-172; P=0.006] and anaemia (haematocrit <33%; AOR 7.5; 95% CI 1.7-32.4; P=0.007) were independent risk factors for MTCT. Placental malaria was associated with a decrease in MTCT (AOR 0.23; 95% CI 0.06-0.89; P=0.034). CONCLUSIONS: IPTp with SP was not associated with a significant impact on MTCT of HIV. Maternal anaemia was an independent risk factor for MTCT.

Role of magnetic resonance imaging and cause of pitfalls in detecting myometrial invasion and cervical involvement in endometrial cancer.

OBJECTIVE: To determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting myometrial invasion and cervical involvement in endometrial cancer. STUDY DESIGN: Seventy two consecutive patients with endometrial carcinoma underwent preoperative MRI. We compared the MRI results with the final histopathological findings. We classify myometrial invasion as <50 or>or=50% and cervical involvement as positive or negative. Standard statistical calculations were used. RESULTS: The sensitivity, specificity, and accuracy of MRI for the detection of myometrial invasion>or=50% were 71, 86, and 58%, respectively. Positive and negative predictive values are 77 and 83%, respectively. The sensitivity, specificity, and accuracy of MRI for the detection of cervical invasion were 41, 97, and 46%, respectively. Positive and negative predictive values are 71 and 89%, respectively. The possible causes of misdiagnosis included a tumor isointense with the myometrium, polypoid tumor, myometrial thinning, exceedingly irregular myometrium, presence of adenomiosis, and presence of leiomyomas. CONCLUSION: MRI assists in planning the surgical treatment of endometrial cancer with an acceptable accuracy and a good specificity, although sensitivity is suboptimal.

Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer. / Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento.

OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.

Familial CD8 deficiency due to a mutation in the CD8 alpha gene.

CD8 glycoproteins play an important role in both the maturation and function of MHC class I-restricted T lymphocytes. A 25-year-old man, from a consanguineous family, with recurrent bacterial infections and total absence of CD8(+) cells, was studied. Ab deficiencies and ZAP-70 and TAP defects were ruled out. A missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene was shown to correlate with the absence of CD8 expression found in the patient and two sisters. Conversely, high percentages of CD4(-)CD8(-)TCR alpha beta(+) T cells were found in the three siblings. A novel autosomal recessive immunologic defect characterized by absence of CD8(+) cells is described. These findings may help to further understanding of the role of CD8 molecules in human immune response.

Comparison of the analytical and clinical performance of five tests for the detection of human papillomavirus genital infection.

HPV-based screening provides greater protection against cervical cancer (CC) than cytology-based strategies. Currently, several molecular diagnostic assays for the detection of human papillomavirus (HPV) are available. In this study, we analyzed 5 different HPV testing and genotyping techniques (Hybrid Capture 2 [HC2; Qiagen, Hilden, Germany], AnyplexTMII HPV28 [Anyplex; Seegene, Seoul, Korea], Linear Array [Roche, Branchburg, NJ, USA], GP5+/6+ PCR-EIA-RH [Labo Bio-medical Products, Rijswijk, The Netherlands] and CLART2 [Genomica, Madrid, Spain]) in 295 women referred to the hospital Colposcopy Clinic from 2007 to 2008 due to positive HPV test results or an abnormal Pap test. DNA extraction for HPV genotyping was performed in cervical sample specimens after Pap test and HPV detection by HC2. The inclusion criteria were: (1) adequate cervical sampling with sufficient material for the Pap test and HPV detection and genotyping, and (2) colposcopically-directed biopsy and/or endocervical curettage. HC2 showed the highest sensitivity for high-grade squamous intraepithelial lesion and CC (HSIL+) detection (96.1%), but all the HPV genotyping tests showed a higher specificity. (Anyplex 86.8%; Linear Array 86.0%; GP5+/6+ 78.8%; CLART2 76.5%). The agreement between HC2 results and the other techniques was similar: 82.4%, kappa=0.650 for Anyplex; 83.4%, kappa=0.670 for Linear Array, 79.93%, kappa=0.609 for GP5+/6+ and 82.4%, kappa=0.654 for CLART2. HPV 16 and/or 18 infection was a risk factor for underlying HSIL+ in the univariate analysis. Anyplex showed the highest risk of underlying HSIL+ after positive HPV 16 and/or 18 tests (OR 31.1; 95% CI 12.1-80.0).

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging.

OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies (aCL) and migraine on 103 consecutive patients with systemic lupus erythematosus (SLE) derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fifty-four (52%) patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty (29%) patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL (17% versus 37%, p = 0.07). No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript.

This report describes an intraabdominal small cell tumor in a 37-year-old woman, with clinical, topographic, and morphologic features highly suggestive of the desmoplastic small round cell tumor. Immunohistochemical analysis revealed a polyphenotypic profile consistent with this tumor--positivity for keratin, epithelial membrane antigen, neuron-specific enolase, vimentin, and desmin--but, in addition, a strong membranous immunoreactivity for CD99 (MIC2 protein). Reverse transcription polymerase chain reaction revealed a EWS/ERG fusion transcript characteristic of the Ewing's sarcoma/peripheral primitive neuroectodermal tumor group of tumors, rather than the EWS/WT1 chimeric transcript typical of the desmoplastic small round cell tumor. This is the third report of a hybrid tumor with features of the desmoplastic small round cell tumor and Ewing's sarcoma/peripheral primitive neuroectodermal tumor, and the first one with the EWS/ERG fusion gene. Our case shows the existence of some overlap between these two groups of tumors, which are considered to be histogenetically different, and the need for further studies of molecular characterization of small cell tumors, especially in those with atypical morphologic or immunohistochemical features.

Mesonephric adenocarcinoma of the uterine corpus: CD10 expression as evidence of mesonephric differentiation.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Massive chronic intervillositis of the placenta associated with malaria infection.

Massive chronic intervillositis (MCI) is an infrequently recognized placental lesion thought to be of immunologic origin that has been associated with poor fetal outcome. It is characterized by a prominent inflammatory infiltrate in the intervillous space, composed mainly of monocytes and macrophages that can simulate a maternal malignant disorder involving the placenta. The villi are characteristically spared. We report 74 cases of placental malarial infection with morphologic features of MCI. In all cases, the massive inflammatory infiltrate was limited to the intervillous space, which appeared largely obliterated. Increased fibrin deposition and prominent syncytial knots were frequent associated findings. Inflammatory cells were CD45 and CD68 positive, consistent with a monocyte-macrophage population. Some polymorphonuclear leukocytes and scattered T and B lymphocytes were also present. Villi were not inflamed. Malarial pigment was present in all cases, and parasitized maternal erythrocytes were evident in 73 of 74 patients. The histologic pattern of MCI was observed in 17.6% of placentas with malarial parasites. Malarial MCI affected predominantly primigravida women (77%) and was associated with a reduced birth weight, which in 39 (53%) of the infants was less than 2500 g, and a low gestational age. None of the infants with placentas with MCI died in the early neonatal period. Morphologic changes of MCI are seen in a significant percentage of placentas with malarial infection, especially in primigravida women, and are associated with a low birth weight. Malarial infection should therefore be considered in the differential diagnosis of massive intervillous infiltrates.

L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

BACKGROUND: To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. METHODS: Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. RESULTS: Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). CONCLUSIONS: L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.